Propionate gluconeogenesis

Cj5 and Cj7 fatty acids are found particularly in the lipids of ruminants. Dietary odd-carbon fatty acids upon oxidation yield propionate (Chapter 22), which is a substrate for gluconeogenesis in human liver. 

Gluconeogenesis is the process of converting noncarbohydrates to glucose or glycogen. It is of particular importance when carbohydrate is not available from the diet. Significant substrates are amino acids, lactate, glycerol, and propionate. 

Propionyl CoA is converted to sucdnyl CoA, a dtric add cyde intermediate, in the two-step propionic add pathway. Because this extra sucdnyl CoA can form malate and enter the cytoplasm and gluconeogenesis, odd-carbon fatty adds represent an exception to the rule that fatty... 

Diabetes - insulin dependent Methyl malonic, propionic or isovaleric acidaemias Pyruvate carboxylase and multiple carboxylase deficiency Gluconeogenesis enzyme deficiency glucose-6-phosphatase, fructose-1,6-diphosphatase or abnormality of glycogen synthesis (glycogen synthase) Ketolysis defects Succinyl coenzyme A 3-keto acid transferase ACAC coenzyme A thiolase... 

Propionate is not a quantitatively significant gluconeogenic precursor in humans, but it is a major source of glucose in ruminants. It is derived from the catabolism of isolecucine, valine, methionine, and threonine from jd-oxidation of odd-chain fatty acids and from the degradation of the side chain of cholesterol. Propionate enters gluconeogenesis via the TCA cycle after conversion to succinyl-CoA (Chapter 18). 

Ruminants can produce massive amounts of glucose from propionate. In cows, the cellulose in grass is converted to propionate by bacteria in the rumen. This substrate is then used to generate more than 5 lb glucose each day by the process of gluconeogenesis. 

In non-ruminant animals, amino acids and lactate form the major sources for gluconeogenesis in ruminant animals, propionate is pre-eminent. Under normal feeding... 

Butyryl-CoA synthetase is active with acids in the range 3-7C and has been isolated from heart mitochondria. It is a mitochondrial enzyme in other tissues but has not been found in liver where a special propionyl-CoA synthetase has been demonstrated. The latter enzyme may be especially important in ruminants where propionate is formed by rumen microorganisms and is an important substrate for gluconeogenesis. 

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